Methods of administering anionic cannabinoid molecules dissolved in water

ABSTRACT

Various aspects of this patent document relate to methods to administer compositions comprising anionic cannabinoid molecules.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent document claims priority to U.S. Provisional PatentApplication No. 62/780,178, filed Dec. 14, 2018, U.S. Provisional PatentApplication No. 62/787,722, filed Jan. 2, 2019, and U.S. ProvisionalPatent Application No. 62/812,849, filed Mar. 1, 2019, each of which isincorporated by reference in its entirety.

BACKGROUND

Cannabinoids that lack a carboxyl group are insoluble in water. Attemptshave been made to suspend cannabinoids in water to produce beverages,for example, by emulsification. Stable emulsions frequently displayunfavorable characteristics such as undesirable flavor and poorbioavailability. Methods to dissolve cannabinoids in water could disruptthe beverage industry.

SUMMARY

Various aspects of this patent document relate to anionic cannabinoidmolecules. Specific aspects of this patent document relate to methods toadminister compositions comprising anionic cannabinoid molecules.

BRIEF DESCRIPTION OF THE DRAWINGS

The FIGURE is a two-dimensional rendering of a three-dimensional modelof2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate(black) bound to four water molecules (grey). Six hydrogen bonds aredepicted with dotted lines.

DETAILED DESCRIPTION

Various aspects of this patent document relate to the discovery thatanionic cannabinoid molecules are water-soluble at mildly-alkaline pH.This discovery was surprising and unexpected because previously-reportedpK_(a) values of various cannabinoids were relatively high. The pK_(a)of cannabidiol has been reported as ranging from 9.13 to 9.64, forexample, and the pK_(a) of tetrahydrocannabinol has been reported as10.6. The present disclosure reveals that the pK_(a)'s of cannabinoidsdissolved in dilute aqueous solution are lower than previously-reportedvalues.

The term “anionic cannabinoid molecule” refers to a cannabinoid moleculethat carries a net negative charge. Anionic cannabinoid moleculesinclude, but are not limited to, cannabinoid molecules that have adeprotonated hydroxyl oxygen such that either (i) the molecule containsan oxide, such as a phenolate, or (ii) a resonance structure of themolecule contains an oxide, such as a phenolate. In some specificembodiments, an anionic cannabinoid molecule is not a carboxylate. Insome very specific embodiments, an anionic cannabinoid molecule lacks acarboxyl or carboxylate.

To determine the pK_(a)'s of cannabinoids in water, cannabinoids weredissolved in water, which was technically challenging as described inthe exemplification section and has never been previously reported. Manyunsuccessful solubilization methods were attempted, some of which aredescribed in the exemplification section, and broadly-applicable methodsthat yield consistent results were eventually developed. Cannabinoidsdissolve in water, for example, after first deprotonating a cannabinoidwith a strong Brønsted base in ethanol and then diluting the ethanolwith water comprising another Brønsted base. The discovery oflower-than-expected pK_(a) values for cannabinoids dissolved in waterallowed the development of beverages containing anionic cannabinoidmolecules, which have surprisingly advantageous properties never-beforeencountered in any consumer product.

Beverages containing anionic cannabinoid molecules have an intense colorat commercially-relevant concentrations, which allows consumers toverify the identity and approximate concentration of an anioniccannabinoid molecule in a product with the unaided eye. The intensecolor rapidly dissipates upon contacting an anionic cannabinoid moleculewith a weak acid such as the carbonic acid of carbonated water or thecitric acid of a Citrus fruit, which allows consumers to readilyauthenticate that a color corresponds to an anionic cannabinoid moleculerather than an adulterant without any analytical devices or reagents.These features are especially useful in the nutritional supplementindustry, for example, because many finished-product manufacturers allowvarying precision and accuracy in the content of their activeingredients. Variable precision or accuracy results in variableefficacy. Unsophisticated manufacturers and unscrupulous manufacturerssimilarly formulate beverages with cannabidiol isolate particles thatlack any bioavailability because humans cannot dissolve, melt, orotherwise digest cannabidiol isolate. The color and color change allownovel marketing by showcasing methods to validate a product, which couldprovide consumer confidence that transcends brand recognition.

Anionic cannabinoid molecules rapidly reprotonate upon ingestion, whichcauses them to adhere to the gastrointestinal lining and favorsabsorption in the mouth, esophagus, and stomach. Historical ingestiblecannabinoid formulations favor absorption in the small intestine, whichprovides significantly slower onset. The effective accessible surfacearea of an anionic cannabinoid molecule formulation is alsoorders-of-magnitude greater than the effective accessible surface areaof historical cannabinoid formulations because dissolved anioniccannabinoids are not sequestered by lipids, surfactants, or emulsifiers.Increased surface area further increases absorption rates. These uniquepharmacokinetic properties allow rapid onset and acute pharmacologicaleffects that have never been previously reported for orally-administeredcannabinoids.

The conjugate base of cannabidiol dissolved in water displays rapid,psychoactive effects less than 5 minutes after ingestion, which isextraordinarily rapid for an orally-administered compound. The rapidonset of pharmacological activity suggests that anionic cannabinoidmolecules are absorbed in the mouth, and possibly through the epitheliallining of the esophagus. Additionally, cannabidiol is not known todisplay a notable psychoactive effect. The rapid absorption of theconjugate base of cannabidiol in the mouth likely results in an abruptbolus of cannabidiol in the blood, which was not previously feasible.Cannabidiol may be marginally psychoactive, and the oral administrationof the conjugate base of cannabidiol might allow the marked perceptionof this psychoactive effect.

Various aspects of this patent document relate to a composition.

Various aspects of this patent document relate to a container comprisinga sealed chamber, in which the container contains a composition in thesealed chamber.

In some embodiments, a composition comprises water and an anioniccannabinoid molecule, in which the anionic cannabinoid molecule isdissolved in the water.

The term “dissolved” refers to a molecule that is a solute of a solventsuch as water. A molecule that is merely suspended within a solvent,such as a molecule of an emulsion, is not dissolved. A cannabinoidmolecule that is non-covalently associated with another cannabinoidmolecule, another lipid, or an amphiphilic molecule within water is notdissolved in the water.

In some embodiments, an anionic cannabinoid molecule is2-[6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.In some specific embodiments, an anionic cannabinoid molecule is2-[1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.

2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

In some embodiments, a composition comprises2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateand2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diolat a molar ratio of 1:10 to 10,000:1. In some specific embodiments, acomposition comprises2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateand2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diolat a molar ratio of 1:1 to 10,000:1. In some very specific embodiments,a composition comprises2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateand2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diolat a molar ratio of 2:1 to 10,000:1.

In some embodiments, a composition comprises water and a plurality ofanionic cannabinoid molecules, and each anionic cannabinoid molecule ofthe plurality of anionic cannabinoid molecules is dissolved in thewater.

In some embodiments, a plurality of anionic cannabinoid moleculescomprises2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateand one or more anionic cannabinoid molecules selected from2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-propylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-3-hydroxy-5-pentylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-3-hydroxy-5-propylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-6-pentyl-1,2-benzoquinone-4-oxide;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-5-pentyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-6-pentyl-1,2-benzoquinone-4-oxide;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-propyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-6-propyl-1,2-benzoquinone-4-oxide;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-5-propyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-6-propyl-1,2-benzoquinone-4-oxide;(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;2-[(2E)-3,7-dimethylocta-2,6-dienyl]-3-hydroxy-5-pentylphenolate; and2-[(2E)-3,7-dimethylocta-2,6-dienyl]-3-hydroxy-5-propylphenolate.

In some embodiments, a composition comprises an anionic cannabinoidmolecule, and the anionic cannabinoid molecule is associated with one ormore counterions in the composition. In some specific embodiments, acomposition comprises an anionic cannabinoid molecule and one or morecounterions selected from potassium ion, sodium ion, magnesium ion, andcalcium ion.

In some embodiments, a composition has a color, and the color is purple.A composition that has a purple color preferentially absorbs yellowfrequencies of light and preferentially transmits violet frequencies oflight such that a human observer observes that the composition is ashade of purple.

In some embodiments, a container contains a composition; the containeris physically associated with a label; and the label comprises an imageof a reference color. In some specific embodiments, a container containsa composition; the container is physically associated with a label; andthe label comprises an image of a reference color to provide a consumeror other individual with a reference to an intended or desired color ofthe composition. In some very specific embodiments, a container containsa composition; the container is physically associated with a label; thelabel comprises an image of a reference color to provide a consumer orother individual with a reference to an intended or desired color of thecomposition; and the reference color is purple. In some very specificembodiments, a container contains a composition; the container isphysically associated with a label; the composition has an actual color;the label comprises an image of a reference color to provide a consumeror other individual with a reference to an intended or desired color ofthe composition; and the actual color corresponds to the referencecolor.

The term “corresponds” refers to approximate identity as perceived by anaverage, unaided human eye such that (i) an actual color corresponds toa reference color if the actual color and the reference color areapproximately the same as perceived by an average, unaided human eye(for example, an unaided human eye may perceive that an actual color anda reference color are both either red, orange, yellow, green, blue, orpurple), (ii) an actual shade corresponds to a reference shade if theactual shade and the reference shade are approximately the same asperceived by an average, unaided human eye (for example, an unaidedhuman eye may perceive that an actual shade of purple and a referenceshade of purple are both either indigo or violet), and (iii) an actualintensity corresponds to a reference intensity if the actual intensityand the reference intensity are approximately the same as perceived byan average, unaided human eye.

In some embodiments, a container contains a composition; the compositionhas an actual color; the actual color has an actual shade; a label isattached to the container; the label comprises an image of a referencecolor to provide a consumer or other individual with a reference to anintended or desired color of the composition; the reference color has areference shade; the actual color corresponds to the reference color;and the actual shade corresponds to the reference shade. In somespecific embodiments, a container contains a composition; thecomposition has an actual color; the actual color is purple; the actualcolor has an actual shade; the actual shade is a shade of purple; alabel is attached to the container; the label comprises an image of areference color to provide a consumer or other individual with areference to an intended or desired color of the composition; thereference color is purple; the reference color has a reference shade;and the reference shade is the shade of purple. In some very specificembodiments, a container contains a composition; the composition has anactual color; the actual color has an actual shade and an actualintensity; a label is attached to the container; the label comprises animage of a reference color to provide a consumer or other individualwith a reference to an intended or desired color of the composition; theactual color corresponds to the reference color; the reference color hasa reference shade and a reference intensity; the actual shadecorresponds to the reference shade; and the actual intensity correspondsto the reference intensity.

In some embodiments, a container contains a composition; the compositionhas an actual color; the actual color has an actual intensity; a labelis attached to the container; the label comprises an image of areference color to provide a consumer or other individual with areference to an intended or desired color of the composition; thereference color has a reference intensity; the actual color correspondsto the reference color; and the actual intensity corresponds to thereference intensity. In some specific embodiments, a container containsa composition; the composition has an actual color; the actual color ispurple; the actual color has an actual intensity; a label is attached tothe container; the label comprises an image of a reference color toprovide a consumer or other individual with a reference to an intendedor desired color of the composition; the reference color is purple; thereference color has a reference intensity; and the actual intensitycorresponds to the reference intensity. In some very specificembodiments, a container contains a composition; the composition has anactual color; the actual color is purple; the actual color has an actualshade; the actual shade is a shade of purple; the actual color has anactual intensity; a label is attached to the container; the labelcomprises an image of a reference color to provide a consumer or otherindividual with a reference to an intended or desired color of thecomposition; the reference color is purple; the reference color has areference shade; the reference shade is the shade of purple; thereference color has a reference intensity; and the actual intensitycorresponds to the reference intensity.

In some embodiments, a composition comprises water and an anioniccannabinoid molecule; and the anionic cannabinoid molecule is dissolvedin the water at a concentration of 20 micrograms per liter to 2000milligrams per liter. In some specific embodiments, an anioniccannabinoid molecule is dissolved in water at a concentration of 100micrograms per liter to 1000 milligrams per liter. In some very specificembodiments, an anionic cannabinoid molecule is dissolved in water at aconcentration of 200 micrograms per liter to 200 milligrams per liter.

In some embodiments, a composition comprises 50 micrograms to 500milligrams of an anionic cannabinoid molecule. In some specificembodiments, a composition comprises 100 micrograms to 100 milligrams ofan anionic cannabinoid molecule.

In some embodiments, a container contains 25 to 800 milliliters of acomposition. In some specific embodiments, a container contains 50 to300 milliliters of a composition. In some specific embodiments, acontainer contains 250 to 600 milliliters of a composition. In somespecific embodiments, a container contains 400 to 800 milliliters of acomposition.

In some embodiments, a composition has a pH, and the pH is 8.5 to 10.5.

In some embodiments, a composition is a liquid, and an anioniccannabinoid molecule is dissolved in the liquid.

In some embodiments, a composition is ice comprising an anioniccannabinoid molecule.

In some embodiments, a composition comprises ethanol at a concentrationof 5 parts per billion to 500 parts per million by weight. In somespecific embodiments, a composition comprises ethanol at a concentrationof 5 parts per million to 500 parts per million by weight. In some veryspecific embodiments, a composition comprises ethanol at a concentrationof 50 parts per million to 500 parts per million by weight.

In some embodiments, a composition comprises a concentration ofmolecular oxygen, and the concentration of molecular oxygen is less than50 micromolar. In some specific embodiments, a composition lacksmolecular oxygen at a concentration greater than 5 micromolar.

In some embodiments, a composition comprises a concentration ofmolecular nitrogen, and the concentration of molecular nitrogen is lessthan 100 micromolar. In some specific embodiments, a composition lacksmolecular nitrogen at a concentration greater than 10 micromolar.

In some embodiments, a composition comprises hydroxide at aconcentration of 1 micromolar to 100 micromolar.

In some embodiments, a sealed chamber is hermetically-sealed.

In some embodiments, a container is a glass bottle, a plastic bottle, oran aluminum can.

In some specific embodiments, a container contains 25 to 800 millilitersof a composition; the composition comprises water and an anioniccannabinoid molecule; the anionic cannabinoid molecule is dissolved inthe water; the composition comprises 50 micrograms to 500 milligrams ofthe anionic cannabinoid molecule; the composition comprises the anioniccannabinoid molecule at a concentration of 100 micrograms per liter to1000 milligrams per liter; the composition has a pH; the pH is 8.5 to10.5; and the anionic cannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.

In some very specific embodiments, a container contains 250 millilitersto 600 milliliters of a composition; the composition comprises water andan anionic cannabinoid molecule; the anionic cannabinoid molecule isdissolved in the water; the composition comprises 200 micrograms to 200milligrams of the anionic cannabinoid molecule; the composition has apH; the pH is 8.5 to 10.5; the anionic cannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate;the composition has a color; the color of the composition is purple; thecontainer comprises a sealed chamber; the container contains thecomposition in the sealed chamber; and the sealed chamber ishermetically-sealed.

Various aspects of this patent document relate to a method to solubilizea cannabinoid in water.

In some embodiments, a method comprises providing a cannabinoidmolecule, in which the cannabinoid molecule comprises an aromatic ringand a hydroxyl group, and the hydroxyl group is a substituent on thearomatic ring. In some specific embodiments, a cannabinoid moleculelacks a carboxyl group.

In some embodiments, a method comprises providing a Brønsted base.

In some embodiments, a method comprises providing water.

In some embodiments, a method comprises contacting a cannabinoidmolecule with a Brønsted base to deprotonate a hydroxyl group of thecannabinoid molecule and to produce an anionic cannabinoid molecule.

In some embodiments, a method comprises dissolving an anioniccannabinoid molecule in water to produce a solution comprising theanionic cannabinoid molecule.

In some embodiments, a cannabinoid molecule is2-[6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol.In some specific embodiments, a cannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol(“cannabidiol”).

In some embodiments, an anionic cannabinoid molecule is2-[6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.In some specific embodiments, an anionic cannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.In some very specific embodiments, a cannabinoid molecule iscannabidiol, and an anionic cannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.

In some embodiments, a cannabinoid molecule is cannabidiol, and ananionic cannabinoid molecule is selected from2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-3-hydroxy-5-pentylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-6-pentyl-1,2-benzoquinone-4-oxide;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-5-pentyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-6-pentyl-1,2-benzoquinone-4-oxide;(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;and(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-oxide.

In some embodiments, a Brønsted base is ethoxide or hydroxide.

In some embodiments, a cannabinoid molecule is dissolved in a solventwhen the cannabinoid molecule is contacted with a Brønsted base.

In some embodiments, a Brønsted base is dissolved in a solvent when theBrønsted base is contacted with a cannabinoid molecule.

In some embodiments, a cannabinoid molecule and a Brønsted base aredissolved in a solvent when the cannabinoid molecule and the Brønstedbase are contacted with each other.

In some embodiments, a solvent is ethanol.

In some embodiments, a solution comprising an anionic cannabinoidmolecule comprises an ethanol concentration, and a method comprisesadjusting the ethanol concentration of the solution to an ethanolconcentration no greater than 0.05% by weight.

In some embodiments, a solvent has a dissolved oxygen concentration, anda method comprises reducing the dissolved oxygen concentration of thesolvent prior to contacting a cannabinoid molecule with a Brønsted base.

In some embodiments, the water of a method has a dissolved oxygenconcentration, and the method comprises reducing the dissolved oxygenconcentration of the water prior to dissolving an anionic cannabinoidmolecule in the water.

In some embodiments, the water of a method has a pH, and the pH isgreater than 9.5.

In some embodiments, a solution comprising an anionic cannabinoidmolecule has a pH, and a method comprises adjusting the pH to 8.5 to10.5.

In some embodiments, a solution comprising an anionic cannabinoidmolecule has a concentration of the anionic cannabinoid molecule, and amethod comprises adjusting the concentration of the anionic cannabinoidmolecule to a concentration of 20 micrograms per liter to 2000milligrams per liter.

In some embodiments, a method results in a lipid phase in fluidcommunication with an aqueous phase that is a solution comprising ananionic cannabinoid molecule, and the method comprises separating thelipid phase from the solution.

In some embodiments, a method comprises freezing a solution comprisingan anionic cannabinoid molecule to produce ice comprising the anioniccannabinoid molecule.

In some embodiments, a method comprises inserting a solution comprisingan anionic cannabinoid molecule into a container and thenhermetically-sealing the container.

In some embodiments, a method comprises inserting 25 milliliters to 800milliliters of a solution comprising an anionic cannabinoid moleculeinto a container.

In some embodiments, a method comprises transferring ownership of acontainer containing a solution comprising an anionic cannabinoidmolecule. In some embodiments, a method comprises receiving payment fortransferring ownership of a container containing a solution comprisingan anionic cannabinoid molecule.

In some embodiments, a method comprises transporting a containercontaining a solution comprising an anionic cannabinoid molecule such asin an intermodal freight container or in a refrigerated van or truck. Insome specific embodiments, a method comprises transporting a containercontaining a solution comprising an anionic cannabinoid molecule, inwhich the container and the solution are refrigerated during thetransporting. In some very specific embodiments, a method comprisesfreezing a solution comprising an anionic cannabinoid molecule toproduce ice comprising the anionic cannabinoid molecule and thentransporting the ice.

In some very specific embodiments, a cannabinoid molecule iscannabidiol; a method comprises contacting the cannabinoid molecule witha Brønsted base; the Brønsted base is dissolved in a solvent when thecannabinoid molecule is contacted with the Brønsted base; the solvent isethanol; the Brønsted base is hydroxide or ethoxide; contacting thecannabinoid molecule with the Brønsted base produces an anioniccannabinoid molecule; the anionic cannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate;the method comprises dissolving the anionic cannabinoid molecule inwater to produce a solution comprising the anionic cannabinoid molecule;the water has a pH; the pH of the water is greater than 9.5; thesolution comprising the anionic cannabinoid molecule has a pH; eitherthe pH of the solution is 8.5 to 10.5, or the method comprises adjustingthe pH of the solution to 8.5 to 10.5; and the method comprisesinserting the solution comprising the anionic cannabinoid molecule intoa container and then hermetically-sealing the container.

Various aspects of this patent document relate to a method ofadministering a cannabinoid. In some embodiments, a method comprisesproviding a composition comprising an anionic cannabinoid moleculedissolved in water and administering the composition to a subject. Insome specific embodiments, a subject is a human being.

Ins some embodiments, an anionic cannabinoid molecule is selected from2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-3-hydroxy-5-pentylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-6-pentyl-1,2-benzoquinone-4-oxide;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-5-pentyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-6-pentyl-1,2-benzoquinone-4-oxide;(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;2-[(2E)-3,7-dimethylocta-2,6-dienyl]-3-hydroxy-5-pentylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-propylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-3-hydroxy-5-propylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-propyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-6-propyl-1,2-benzoquinone-4-oxide;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-5-propyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-6-propyl-1,2-benzoquinone-4-oxide;(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;and 2-[(2E)-3,7-dimethylocta-2,6-dienyl]-3-hydroxy-5-propylphenolate. Insome specific embodiments, an anionic cannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-3-hydroxy-5-pentylphenolate.

In some embodiments, administering a composition comprises oral,self-administration performed by a subject by drinking the composition.

In some embodiments, a method comprises providing a hermetically-sealedcontainer containing a composition and unsealing the container toprovide the composition. In some specific embodiments, ahermetically-sealed container contains 25 milliliters to 800 millilitersof a composition. In some specific embodiments, a hermetically-sealedcontainer contains 50 micrograms to 500 milligrams of an anioniccannabinoid molecule. In some specific embodiments, ahermetically-sealed container is a glass bottle, plastic bottle, oraluminum can.

In some embodiments, a composition comprises an anionic cannabinoidmolecule; the composition has an actual color; a container contains thecomposition; the container is physically associated with a label; thelabel comprises an image of a reference color; and a method comprisescomparing the actual color with the reference color to either confirmthe identity of the anionic cannabinoid molecule or confirm theapproximate concentration of the anionic cannabinoid molecule in thecomposition.

In some embodiments, a composition has a color, and the color is purple.

In some embodiments, a composition has a color; a method comprisescontacting the composition with a Brønsted acid prior to administeringthe composition; and contacting the composition with the Brønsted acidchanges the color to either a different color or no color.

In some embodiments, a Brønsted acid is carbonic acid or citric acid. Insome specific embodiments, contacting a composition with a Brønsted acidcomprises contacting the composition with a carbonated liquid comprisingcarbonic acid. In some specific embodiments, contacting a compositionwith a Brønsted acid comprises contacting the composition with a juicefrom a Citrus fruit, in which the juice comprises citric acid. In somevery specific embodiments, contacting a composition with a Brønsted acidcomprises contacting the composition with a lemon, a lime, a juice of alemon, or a juice of a lime.

In some embodiments, a composition has a pH, and the pH is 8.5 to 10.5.

In some embodiments, a composition comprises ethanol at a concentrationof 5 parts per million to 500 parts per million by weight.

In some embodiments, a composition comprises a concentration ofmolecular oxygen, and the concentration of molecular oxygen is less than50 micromolar. In some specific embodiments, a composition lacksmolecular oxygen at a concentration greater than 5 micromolar.

In some embodiments, a composition comprises a concentration ofmolecular nitrogen, and the concentration of molecular nitrogen is lessthan 100 micromolar. In some specific embodiments, a composition lacksmolecular nitrogen at a concentration greater than 10 micromolar.

In some specific embodiments, a method comprises: providing ahermetically-sealed container containing a composition comprising bothwater and an anionic cannabinoid molecule that is dissolved in thewater; unsealing the hermetically-sealed container to provide thecomposition; and administering the composition to a subject, in which:the hermetically-sealed container is a glass bottle, plastic bottle, oraluminum can; the container contains 25 milliliters to 800 millilitersof the composition; the container contains 50 micrograms to 500milligrams of the anionic cannabinoid molecule; the anionic cannabinoidmolecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate;the composition has a pH; the pH of the composition is 8.5 to 10.5; thesubject is a human being; and administering the composition is oral,self-administration performed by the subject by drinking thecomposition.

The words “comprising,” “comprises,” and “comprise” refer to open-endedsets. For example, a composition comprising water can also compriseethanol.

The following exemplification section provides a framework to implementcertain aspects of the disclosure, and the exemplification does notlimit the scope of this patent document or any claim that matures fromthis patent document.

EXEMPLIFICATION

The experiments described in the following examples were initiallyperformed to determine whether the conjugate base ofcannabidiol—2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate—couldbe used to purify cannabidiol from tetrahydrocannabinol and otherneutrally-charged lipids. It was contemplated that either (i) theproduction of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein an aqueous phase would allow the mechanical separation of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatefrom a lipid phase containing tetrahydrocannabinol and otherneutrally-charged lipids such as in a separatory funnel or such as bycentrifugal partition chromatography, or (ii) the production of a2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatesalt would allow the separation of the2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatesalt from tetrahydrocannabinol and other volatile molecules byvaporizing the tetrahydrocannabinol and other volatile molecules. Theseexperiments were not expected to result in useful compositions andmethods, however, because the deprotonation of cannabidiol was thoughtto cause oxidation. The following experiments were neverthelessperformed with the hope of identifying purification methods capable ofout competing oxidation.

Examples 1-15 describe representative experiments that generatednegative results.

Examples 16-18 describe successful proof-of-concept experiments.

Following the successful proof-of-concept experiments, the approximatepK_(a) of cannabidiol in water was determined. Various pK_(a)'s havebeen reported and range from 9.13 to 9.64. If the pK_(a) of cannabidiolwere 9.13, which was the lowest previously-reported pK_(a) forcannabidiol, then cannabidiol might be expected to lack stability inwater at a pH of 9.5 because approximately 30% of the dissolvedcannabidiol and2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewould exist as cannabidiol, which might form a lipid phase. This lipidphase would be a thermodynamic sink if the lipid phase were to separatefrom the aqueous phase. Le Châtelier's principle could drive theconversion of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateinto cannabidiol until the composition existed as an aqueous phaseessentially devoid of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateand a lipid phase comprising cannabidiol. A greater pK_(a), such as apK_(a) of 9.64, would magnify this detrimental effect. Examples 7 and 8are consistent with the reported pK_(a)'s.

Example 19 unexpectedly suggested that the pK_(a) of cannabidiol inwater is substantially lower than all previously-reported values. Thisfinding suggested for the first time that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatemight be viable for inclusion in beverages.

Example 20 confirms that the pK_(a) of cannabidiol in water is lowerthan all previously-reported pK_(a) values.

Example 21 confirms that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateis stable in commercially-relevant embodiments.

Example 22 describes a molecular model of a dissolved state of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein water, which might account for the unexpected pK_(a) of cannabidiolin water.

Example 23 describes unexpectedly superior pharmacokinetic properties of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatedissolved in water relative to cannabidiol.

Example 24 provides third-party test results that confirm the stabilityand concentration of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatedissolved in water.

The findings described in this section reveal that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateis not only a viable intermediate for use in purification methods, but2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateis also viable for inclusion in beverages. These findings are generallyapplicable to all known and yet-to-be-described cannabinoids thatinclude an aromatic ring containing a hydroxyl substituent.

Example 1. Combining Crude Industrial Hemp Extract with PotassiumHydroxide Alone Does Not Produce2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

30 grams of potassium hydroxide was added to 155 grams of crudeindustrial hemp extract containing approximately 65% cannabidiol. Thecomposition was stirred at 55° C. for 30 minutes. The potassiumhydroxide remained present as white solid, and no color changeindicative of a conversion from cannabidiol to2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewas apparent. An aliquot of the composition was incubated overnight at55° C., and no dissolution of the potassium hydroxide or color changewas apparent.

Example 2. Combining Crude Industrial Hemp Extract with PotassiumHydroxide in an Approximate Equal-Volume of Water Does Not Produce anAppreciable Amount of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

155 grams of distilled water was added to the mixture prepared inExample 1, and the composition was stirred at 55° C. for 30 minutes. Thepotassium hydroxide dissolved, and a purple sheen became apparent in themixture, which suggests that at least some of the cannabidiol convertedto2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The mixture was incubated overnight at 55° C. to separate the aqueousphase from the lipid phase. The mixture was then cooled to solidify thelipid phase, and the aqueous phase and lipid phase were mechanicallyseparated. Residual water was blotted from the lipid phase, and thelipid phase was further dehydrated in an oven. Visual examination of thelipid phase revealed a nominal purple layer on the surface of an amplebrown core, which indicates that the experiment produced a minimalamount of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatethat separated from the remaining crude industrial hemp extract.

Example 3. Combining Crude Industrial Hemp Extract with PotassiumHydroxide in Excess Water Does Not Produce an Appreciable Amount of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

1.55 grams of crude industrial hemp extract comprising approximately 65%cannabidiol was suspended in 1.55 liters of distilled water to which 3grams of potassium hydroxide was added. The suspension was vigorouslystirred at 95° C. for 30 minutes in a closed flask. The pH of thesuspension was determined to be only slightly alkaline, and so, a secondaliquot of 3 grams of potassium hydroxide was added to the suspension.The suspension was vigorously stirred overnight at 55° C. The suspensionwas then allowed to separate with gentle stirring at 55° C., and thelipid phase floated to the top. The aqueous phase lacked a purple colorindicative of a conversion from cannabidiol to2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.

Example 4. Combining Cannabidiol Isolate with Potassium Hydroxide inWater Produces an Unknown Side Product

1 gram of cannabidiol isolate was vigorously mixed with 2.5 millilitersof water and excess potassium hydroxide at 95° C. The mixture initiallyformed a light purple lipid phase and a light purple aqueous phase. Thepurple lipid phase eventually formed crystals, and, after additionalmixing at 95° C., the lipid phase formed a purple, semisolid mass. Thesemisolid mass was rinsed with water. 0.72 grams of the semisolid masswas dissolved in 1.5 milliliters of ethanol, and 0.17 grams of citricacid was added to the solution. The solution formed a reddish-brownliquid phase, which indicates that the experiment produced an unknownproduct.

Example 5. Combining Cannabidiol Isolate with Potassium Hydroxide inGlycerol Produces an Unknown Side Product

1 gram of potassium hydroxide was dissolved in 50 milliliters ofglycerol with heating. 2.3 milliliters of the potassium hydroxidesolution was added to 230 milligrams of cannabidiol isolate, and themixture was heated with stirring. The cannabidiol did not completelydissolve in the glycerol, and so, 6.9 additional milliliters of thepotassium hydroxide solution was added to the mixture. The cannabidiolthen dissolved, and the solution became salmon-colored, which indicatesthat the experiment produced an unknown product.

Example 6. Combining Cannabidiol Isolate with Potassium Hydroxide inEthanol Produces2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

500 milligrams of cannabidiol isolate was dissolved in 5 milliliters of350 millimolar potassium hydroxide in ethanol. The cannabidiol wasdeprotonated to form2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateas evidenced by a strong purple color.

1 milliliter of the2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatesolution was added to a 500 milliliter bottle of FIJI® natural artesianwater. The addition of the2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateto FIJI® water resulted in a color change from purple to colorless andresulted in an emulsion as evidenced by visual observation of the ouzoeffect.

FIJI® water contains bicarbonate, which is a Brønsted acid that couldre-protonate the2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.1 milliliter of the2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatesolution was therefore also added to a 296 milliliter bottle of DASANI®purified water. The addition of the2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateto DASANI® water resulted in a color change from purple to colorless andresulted in an emulsion as evidenced by visual observation of the ouzoeffect. The pH of the emulsion in DASANI® water was determined to bestrongly alkaline.

These experiments suggest that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein ethanol cannot be directly added to drinking water to produce afinished beverage.

Example 7. Attempt to Adjust the pH of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatePrepared From Filtered Industrial Hemp Extract

1.65 grams of carbon-filtered industrial hemp extract comprisingapproximately 65% cannabidiol was dissolved in 10 milliliters of 420millimolar potassium hydroxide in ethanol to convert the cannabidiolinto2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewas then diluted with 90 milliliters of 100 millimolar sodium carbonatein water, which resulted in an emulsion as evidenced by visualobservation of the ouzo effect. The pH of the emulsion was adjusted to9.1 with 300 milliliters of 500 millimolar sodium bicarbonate, whichresulted in the conversion of the2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateback into cannabidiol as evidenced by a color change and separation of alipid phase. This experiment suggested that the pK_(a) of cannabidiol inwater is greater than 9.1.

Example 8. Attempt to Adjust the pH of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatePrepared From Cannabidiol Isolate

1 gram of cannabidiol isolate was dissolved in 10 milliliters of 380millimolar potassium hydroxide in ethanol to convert the cannabidiolinto2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewas then diluted with 90 milliliters of 100 millimolar sodium carbonatein water, which resulted in an emulsion as evidenced by visualobservation of the ouzo effect. The pH of the emulsion was adjusted to9.1 with 300 milliliters of 0.5 molar sodium bicarbonate, which resultedin the conversion of the2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateback into cannabidiol as evidenced by a color change and separation of alipid phase. This experiment suggested that the pK_(a) of cannabidiol inwater is greater than 9.1.

Example 9. Attempt to Centrifuge an Emulsion Comprising2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

1.65 grams of carbon-filtered industrial hemp extract comprisingapproximately 65% cannabidiol was dissolved in 10 milliliters of 420millimolar potassium hydroxide in ethanol to convert the cannabidiolinto2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewas then diluted with 80 milliliters of 110 millimolar sodium carbonatein water, which resulted in an emulsion as evidenced by visualobservation of the ouzo effect. The emulsion was centrifuged in anunsuccessful attempt to phase-separate the emulsion.

Example 10. Attempt to Prepare2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateFrom Crude Industrial Hemp Extract

33.3 grams of crude industrial hemp extract comprising approximately 65%cannabidiol was dissolved in 50 milliliters of 2.5 molar potassiumhydroxide in ethanol to convert the cannabidiol into2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The solution was diluted into 450 milliliters of 100 millimolar aqueouspotassium hydroxide, and the solution rapidly formed an emulsion.

Example 11. Attempt to Prepare2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateFrom Industrial Hemp Extract

The experiment of Example 10 was repeated, but the 100 millimolaraqueous potassium hydroxide was added to the 50 milliliters of 2.5 molarpotassium hydroxide in ethanol solution containing the 33.3 grams of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate(rather than adding the ethanol solution to the aqueous potassiumhydroxide). This time, the solution did not appear to form an emulsion.The solution was added to 2000 milliliters of 1 molar sodium bicarbonatesolution having a pH adjusted to 8.8 with potassium hydroxide, and thebuffered solution formed an emulsion. This experiment suggests that itmay be possible to dissolve2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein water, but it might not be possible to buffer a solution of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein water.

Example 12. Attempt to Prepare2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateFrom Cannabidiol Isolate

The experiment of Example 11 was repeated with cannabidiol isolate. 6.6grams of cannabidiol isolate was dissolved in 10 milliliters of 2.5molar potassium hydroxide in ethanol to convert the cannabidiol into2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.90 milliliters of 100 millimolar aqueous potassium hydroxide was addedto the2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein ethanol solution with stirring, and the solution formed an emulsion.

Example 13. Attempt to Prepare2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateFrom Cannabidiol Isolate

The experiment of Example 12 was repeated at a 1-to-5 dilution. 1.4grams of cannabidiol isolate was dissolved in 10 milliliters of 0.5molar potassium hydroxide in ethanol to convert the cannabidiol into2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.90 milliliters of 100 millimolar aqueous sodium bicarbonate was added tothe2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein ethanol solution with stirring, and the solution formed an emulsion.

Example 14. Attempt to Water-Solubilize2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateFrom a Potassium Salt

1.4 grams of pure cannabidiol was dissolved in 10 milliliters of 0.5molar potassium hydroxide in ethanol to convert the cannabidiol into2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.A potassium salt of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewas formed by drying the ethanol solution under vacuum overnight. 90milliliters of 100 millimolar aqueous sodium carbonate was added to thepotassium salt of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.A portion of the potassium salt of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatedissolved, but the majority of the salt remained in the solid phase.This experiment suggests that it might not be possible to dissolve anappreciable amount of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein water.

Example 15. Removal of Ethanol From2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein a Vacuum Oven Produces an Unknown Side Product

372 grams of crude industrial hemp extract containing approximately 65%cannabidiol was dissolved in ethanol at a weight ratio of 1:2 crude toethanol. 43.2 grams of potassium hydroxide was slowly added to the hempextract in ethanol, and the solution was stirred while heating at 55° C.The solution was then placed in an oven under vacuum and slowly rampedto a temperature of 157° C. over the course of approximately 1 hour, atwhich time heating was discontinued. The solution was then left in theoven under vacuum overnight.

The product produced by ethanol removal in an oven under vacuum waspurple with a taffy-like consistency indicative of polymer formation.The product lacked appreciable solubility in water. This experimentsuggests that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateis unstable at high temperatures.

Example 16. Preparation of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateDissolved in Water

This example describes the first successful attempt to solubilize2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein water. 0.5 grams of cannabidiol was dissolved in 3.3 milliliters of0.5 molar potassium hydroxide in ethanol to produce2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The conversion of cannabidiol to2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewas readily confirmed by color because cannabidiol lacks discernablecolor and2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatehas a deep purple color.

The2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewas diluted with 26.7 milliliters of 100 millimolar sodium carbonate inwater. The mixture produced an emulsion as evidenced by visualobservation of the ouzo effect. Centrifugation was attempted tophase-separate the emulsion, and phase separation was surprisinglysuccessful (compare with Example 9). This example differs from Example 9in that this example used cannabidiol isolate, which had a puritygreater than 95% by weight, relative to the industrial hemp extract ofExample 9, which had a purity of approximately 65% by weight. Thesupernatant was divided into three aliquots of 10 milliliters each foruse in other experiments.

Example 17. Preparation of Salts Comprising2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

This example describes a successful attempt to produce a salt of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatethat readily dissolves in water. A first aliquot from Example 16 waslyophilized to produce salts including a potassium2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatesalt and a sodium2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatesalt. The lyophilized salt was added to distilled water, and a portionof the salt immediately dissolved in the water as evidenced by a colorchange from transparent colorless to transparent purple. The water wascentrifuged to remove undissolved salt and to produce an aqueoussolution of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateconcentrate for inclusion in beverages.

Example 18. Reconstituting Cannabidiol From2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

0.1 milliliters of 5 molar citric acid was added to an aliquot fromExample 16 to reconstitute cannabidiol from2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The reconstitution of cannabidiol was confirmed by color.

Example 19. Determining that the pK_(a) of Cannabidiol in Water is Lowerthan Previously Reported

1 gram of cannabidiol was dissolved in 6.6 milliliters of 0.5 molarpotassium hydroxide in ethanol to produce2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The solution was then diluted with 100 millimolar sodium carbonate inwater to a final volume of 50 milliliters to produce a solutioncomprising2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateat approximately 20-grams-per-liter. 0.5 milliliters of the2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatesolution was added to each of 25 test tubes containing 9.5 millilitersof 100 millimolar (0.1 M) carbonate/bicarbonate (CO₃ ²⁻/HCO₃ ⁻) bufferaccording to Table 1. Each test tube contained approximately 10milligrams of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateat a concentration of approximately 1 gram-per-liter. pH's wereconfirmed by multiple different measurements.

TABLE 1 Aqueous compositions comprising 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3- hydroxy-5-pentylphenolateat variable pH Sample pH 0.1M CO₃ ²⁻* 0.1M HCO₃ ⁻ 1 9.1 0.06 mL 8.94 mL2 9.2 0.20 mL 8.80 mL 3 9.3 0.36 mL 8.64 mL 4 9.4 0.56 mL 8.44 mL 5 9.50.80 mL 8.20 mL 6 9.6 1.08 mL 7.92 mL 7 9.7 1.41 mL 7.59 mL 8 9.8 1.78mL 7.22 mL 9 9.9 2.21 mL 6.79 mL 10 10.0 2.67 mL 6.33 mL 11-13 10.3 4.25mL 4.75 mL 14-16 10.4 4.79 mL 4.21 mL 17-19 10.5 5.32 mL 3.68 mL 20-2211.0 7.42 mL 1.58 mL 23-25 11.5 8.44 mL 0.56 mL *The amount of CO₃ ²⁻ inTable 1 does not include the approximately 0.5 milliliters of 100millimolar sodium carbonate that was added with the 0.5 milliliters of20 gram-per-liter solution of 2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.

It was expected that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewould reform cannabidiol at pH's below a threshold pH as evidenced by anexpected color change from purple (indicative of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate)to colorless (indicative of cannabidiol). No color change occurred atpH's of 9.1 and above. This finding suggested for the first time thatthe pK_(a) of cannabidiol is less than 9.1 in dilute aqueous solutionsand that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateis a viable ingredient for inclusion in beverages.

Example 20. Determining the Approximate pK_(a) of Cannabidiol

This example confirms that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateis viable for inclusion in beverages formulated for human consumption.0.5 milliliters of the 20 gram-per-liter solution of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatedescribed in Example 19 was diluted with 9.5 milliliters of distilledwater comprising varying concentrations of sodium bicarbonate, and colorwas monitored as shown in Table 2. pH's were confirmed by multipledifferent measurements.

TABLE 2 Samples used to determine an approximate pK_(a) for cannabidiolNaHCO₃ concentration Sample pH in millimolar color 26 8.0 1000 faintpurple 27 8.3 500 light purple 28 8.6 250 Purple 29 8.9 125 Purple 309.2 62 Purple

A color change was visually apparent at a pH of 8.0, and a subtle colorchange was visually apparent at pH of 8.3. These findings suggest thatthe pK_(a) of cannabidiol in dilute aqueous solution is between 8.0 and8.5. This result was surprising given that previously-reported pK_(a)'sfor cannabidiol range from 9.13 to 9.64 and because thechemically-related molecule resorcinol has a pK_(a) of 9.15. Further,even though sample 26, which had a pH of 8.0, displayed a color changeindicative of conversion from2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateto cannabidiol, no lipid phase formed, which suggests that theinterconversion between2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateand cannabidiol in aqueous solution can kinetically trap cannabidiol inthe aqueous phase and inhibit the production of a lipid phase. Thesefindings suggest that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate,the conjugate base of cannabidiol, is suitable for use in beverages forhuman consumption.

Example 21. Confirming the Commercial Viability of Beverages Comprising2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

20 milliliters of water was removed from a 1 liter bottle of ESSENTIA®OVERACHIEVING H₂O®. ESSENTIA® OVERACHIEVING H₂O® contains purifiedwater, sodium bicarbonate, dipotassium phosphate, magnesium sulfate, andcalcium chloride, and its pH was determined to be about 9.5. The 20milliliters of removed water was replaced with 20 milliliters of the 20gram-per-liter solution of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate,which is described in Example 19, and the bottle was sealed using thescrew-cap top of the bottle to produce a sealed container containingapproximately 400 milligrams of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The pH of the liquid was measured and determined to be about 10. Theliquid was purple and transparent.

5 milliliters of water was removed from a 500 milliliter bottle ofDASANI® purified water. DANSANI® purified water contains purified water,magnesium sulfate, potassium chloride, and sodium chloride, and its pHwas determined to be about 7.0. The 5 milliliters of removed water wasreplaced with 5 milliliters of the 20 gram-per-liter solution of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate,which is described in Example 19, and the bottle was sealed using thescrew-cap top of the bottle to produce a sealed container containingapproximately 100 milligrams of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The pH of the liquid was measured and determined to be about 9.5. Theliquid was transparent and purple.

0.5 milliliters of water was removed from a 500 milliliter bottle ofDASANI® purified water. The 0.5 milliliters of removed water wasreplaced with 0.5 milliliters of the 20 gram-per-liter solution of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate,which is described in Example 19, and the bottle was sealed using thescrew-cap top of the bottle to produce a sealed container containingapproximately 10 milligrams of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The pH of the liquid was measured and determined to be about 8.5. Theliquid was transparent and lacked discernable color.

The preceding experiments confirm that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateis suitable for use in commercially-relevant beverages.

Example 22. Molecular Model of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate

2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewas modeled in three dimensions to identify molecular features thatmight result in a lower pK_(a) than resorcinol and other relatedmolecules. Two water molecules are capable of hydrogen bonding with the1-oxide oxygen of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateand the pi cloud of its 4-carbon, which carries a partial negativecharge from its keto-resonance structures (The FIGURE, fourth and secondgrey water molecules from the left, respectively). These two watermolecules can hydrogen-bond with a third water molecule (The FIGURE,third grey water molecule from the left) with bond lengths and bondgeometries that are similar to those found in ice, which indicates astrong likelihood of stable coordination of water by2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.The oxygen atom of the third water molecule would be about 3.0 to 3.5angstroms away from the 2-carbon of the cyclohexenyl group, and the2-proton would be nearly in-line with the line connecting the wateroxygen and the 2-carbon, which suggests a favorable interaction similarto a hydrogen bond (not shown). A fourth water molecule (The FIGURE,first grey water molecule from the left) can connect the three otherwaters to the 3-hydroxyl of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateby forming two additional hydrogen bonds.

The FIGURE shows that four coordinated water molecules can directlyconnect the 1-oxide of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewith its 3-hydroxyl through a chain of hydrogen bonds. In thisconfiguration, the protonation of the 1-oxide oxygen is disfavored, andprotonation could nevertheless result in the deprotonation of the3-hydroxyl group, thereby regenerating2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.Specifically, the protonation of the 1-oxide oxygen could deprotonate abound water (The FIGURE, fourth grey water molecule from the left),which could deprotonate a second bound water (The FIGURE, third greywater molecule from the left), which could deprotonate a third boundwater (The FIGURE, second grey water molecule from the left), whichcould deprotonate a fourth bound water (The FIGURE, first grey watermolecule from the left), which could deprotonate the 3-hydroxyl group,to regenerate2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.Each of these four, bound waters displays near-ideal bond lengths andbond geometries in the model depicted in The FIGURE, which suggests thatthis configuration and similar configurations contribute to theunexpected, surprising stability of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein water at pH's ranging from 8.5 to 10.5.

Example 23. Qualitative Assessment of the Pharmacokinetics of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein Humans

Approximately 60 milligrams of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateprepared from crude industrial hemp extract was dissolved in water asdescribed in Example 16, buffered to a pH of 9.1, and added to a 296milliliter bottle of DASANI® purified water. The resultant solution wastransparent, had a purple color, and had an approximate concentration of200 milligrams per liter. A healthy, consenting adult self-administeredthe entire bottle of 60 milligrams of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatein water orally over 5 to 10 minutes. The individual reportedexperiencing the rapid onset of a perceptible psychoactive effect withinminutes of ingestion followed by a marked perceptible psychoactiveeffect approximately 30 minutes following ingestion. The individualdescribed the psychoactive effect as a pleasant sensation accompanied byboth an enhanced ability to focus and elevated alertness.

Approximately 30 milligrams of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateprepared from crude industrial hemp extract was dissolved in water,buffered to a pH of 9.1, and added to each of four 296 milliliterbottles of DASANI® purified water. The resultant solutions weretransparent, had a purple color, and approximate concentrations of 100milligrams per liter. Four healthy, consenting adults orallyself-administered varying amounts of the four solutions over 5 to 10minutes. Three of the four individuals reported experiencing a rapidonset of a perceptible psychoactive effect similar to the psychoactiveeffect described above within minutes of ingestion.

This example is consistent with the hypothesis that2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateis rapidly converted into cannabidiol upon contacting the oral mucosaand that at least some of the cannabidiol adheres to the epitheliallining of the buccal cavity, and possibly the esophagus, through whichthe cannabidiol is rapidly absorbed. Any2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatethat reaches the stomach would be quickly converted into cannabidiol byhydronium ion, and the cannabidiol would similarly favor adherence tothe epithelial lining of the stomach followed by rapid absorption. Thisdigestive mechanism is inapposite to the digestion of cannabidiol invegetable oil carriers, in which the cannabidiol would be expected toremain sequestered within a lipid phase that would be expected to floaton the surface of the gastric juice until gastric emptying, after whichthe lipases of the small intestine could hydrolyze the lipids forabsorption of the cannabidiol through the epithelial lining of the smallintestine.

2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatedissolved in water has multiple pharmacokinetic advantages overcannabidiol dissolved in vegetable oils, including (i) increasedeffective surface area, (ii) absorption through the epithelial lining ofthe mouth, which bypasses first-pass metabolism and allows rapidpharmacological effects, (iii) absorption in the stomach, which allowsrapid pharmacological effects relative to absorption in the smallintestine, and (iv) avoidance of digestive enzymes, including thedigestive enzymes of the small intestine.2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatedissolved in water delivers a more reproducible bolus of cannabidiolrelative to cannabidiol dissolved in a vegetable oil carrier for thereasons described above.2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatedissolved in water delivers a larger effective amount of cannabidiolrelative to the same amount of cannabidiol dissolved in a vegetable oilcarrier for the reasons described above.

Example 24. Confirmation of2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateDissolved in Water by an Accredited, Third-Party Laboratory

Pure cannabidiol was deprotonated and dissolved in water using astrategy similar to those described in Examples 16 and 19. Acetic acidwas then added to 100 milliliters of the water, dropwise, until thepurple color disappeared to reform cannabidiol. Reprotonated cannabidiolwas extracted from the water using 4 milliliters of olive oil. Two 1milliliter samples of the olive oil were sent to Botanacor Laboratories(Boulder, Colo.) for cannabinoid profile analysis using an AgilentTechnologies (Santa Clara, Calif.) High Performance LiquidChromatography instrument with a diode array detector. BotanacorLaboratories is ISO/IEC 17025 accredited for cannabinoid potencydetermination. Botanacor Laboratories determined that the two olive oilsamples contained 0.18% and 0.21% cannabidiol by weight and did notdetect any other cannabinoid in the samples. This experiment suggeststhat2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolatewas dissolved in water at a concentration of about 78 milligrams perliter.

1. A composition, comprising2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolateand2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diolat a molar ratio of 1:10 to 10,000:1. 2-3. (canceled)
 4. A method ofconsuming a cannabinoid, comprising: providing a composition comprisingan anionic cannabinoid molecule dissolved in water, in which thecomposition has a color; contacting the composition with a Brønstedacid, in which contacting the composition with the Brønsted acid changesthe color to either a different color or no color; and consuming thecomposition after contacting the composition with the Brønsted acid, inwhich a human being consumes the composition by drinking it.
 5. Themethod of claim 4, in which the anionic cannabinoid molecule is selectedfrom:2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-3-hydroxy-5-pentylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-6-pentyl-1,2-benzoquinone-4-oxide;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-5-pentyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-6-pentyl-1,2-benzoquinone-4-oxide;(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;(6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;2-[(2E)-3,7-dim ethyl octa-2,6-dienyl]-3-hydroxy-5-pentylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-propylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-3-hydroxy-5-propylphenolate;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-propyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-6-propyl-1,2-benzoquinone-4-oxide;2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-5-propyl-1,4-benzoquinone-3-oxide;3-[(1R,6R)-6-isopropenyl-3-methylcyclohex-3-en-1-yl]-6-propyl-1,2-benzoquinone-4-oxide;(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;(6aR,10aR)-6,6,9-trimethyl-3-propyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-oxide;and 2-[(2E)-3,7-dimethylocta-2,6-dienyl]-3-hydroxy-5-propylphenolate. 6.The method of claim 5, in which the anionic cannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.7-8. (canceled)
 9. The method of claim 4, comprising providing ahermetically-sealed container that contains the composition andunsealing the container to provide the composition.
 10. The method ofclaim 9, in which the hermetically-sealed container contains 25milliliters to 800 milliliters of the composition.
 11. The method ofclaim 9, in which the composition comprises 50 micrograms to 500milligrams of the anionic cannabinoid molecule.
 12. The method of claim9, in which the hermetically-sealed container is a glass bottle, plasticbottle, or aluminum can.
 13. The method of claim 9, in which: thehermetically-sealed container is physically associated with a label; thelabel comprises an image of a reference color; and the method comprisescomparing the color to the reference color to either confirm theidentity of the anionic cannabinoid molecule or confirm the approximateconcentration of the anionic cannabinoid molecule in the composition.14. The method of claim 4, in which the color is purple.
 15. (canceled)16. The method of claim 4, in which the composition has a pH, and the pHis 8.5 to 10.5.
 17. The method of claim 4, in which the compositioncomprises ethanol at a concentration of 5 parts per million to 500 partsper million by weight.
 18. The method of claim 4, in which thecomposition comprises a concentration of molecular oxygen, and theconcentration of molecular oxygen is less than 50 micromolar.
 19. Themethod of claim 18, in which the composition comprises a concentrationof molecular nitrogen, and the concentration of molecular nitrogen isless than 100 micromolar.
 20. The method of claim 4, comprisingproviding a hermetically-sealed container containing the composition andunsealing the container to provide the composition, in which: thehermetically-sealed container is a glass bottle, plastic bottle, oraluminum can; the container contains 25 milliliters to 800 millilitersof the composition; the composition comprises 50 micrograms to 500milligrams of the anionic cannabinoid molecule; the anionic cannabinoidmolecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate;the composition has a pH; and the pH of the composition is 8.5 to 10.5.21. A method of consuming a cannabinoid, comprising: providing ahermetically-sealed container that contains a composition, in which: thehermetically-sealed container is a glass bottle, plastic bottle, oraluminum can; the container contains 25 milliliters to 800 millilitersof the composition; the composition comprises water and 50 micrograms to500 milligrams of an anionic cannabinoid molecule; the anioniccannabinoid molecule is dissolved in the water; and the composition hasa color; unsealing the container; contacting the composition with aBrønsted acid, in which contacting the composition with the Brønstedacid changes the color to either a different color or no color; andconsuming the composition after contacting the composition with theBrønsted acid, in which a human being consumes the composition bydrinking it.
 22. The method of claim 21, in which the anioniccannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate.23. The method of claim 21, in which the color is purple.
 24. The methodof claim 21, in which the anionic cannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate;and the color is purple.
 25. A method to change the color of acomposition, comprising: providing a container that contains acomposition, in which: the composition comprises an anionic cannabinoidmolecule dissolved in water; the anionic cannabinoid molecule is2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-3-hydroxy-5-pentylphenolate;the composition has a color; and the color is purple; and contacting thecomposition with a Brønsted acid, in which contacting the compositionwith the Brønsted acid changes the color from purple to either adifferent color or no color.